AN INFORMATIONAL GUIDE

The goal of treatment is to reduce or

eliminate seizures and to minimize

their impact on development.3,4

6% of children with epilepsy under

3 years1

PREVALENCE*

Dravet syndrome persists

throughout the patient’s life1

1 in 15,700 infants2

INCIDENCE*

DRAVET SYNDROME

The acute onset of seizures in a developmentally normal infant can signify Dravet syndrome,

a severe treatment-resistant epilepsy.3,5

A rare and severe genetic epilepsy syndrome6:

• 70% to 85% of patients present with mutations in the SCN1A sodium channel gene3,6

• >100 known sodium channel mutations7

Presence of mutation without clinical signs is not sufficient for diagnosis and absence of mutation does not exclude diagnosis of Dravet.6

*May be higher with increased use of genetic testing.

AN INFORMATIONAL GUIDE

INFANCY

BIRTH

2 YEARS

The initial seizure is often triggered by an illness and may present as a prolonged generalized or hemiclonic seizure.3,5

Initial EEGs and MRIs are often normal.3

DRAVET SYNDROME HAS DISTINCT CHARACTERISTICS TO CONFIRM DIAGNOSIS

CLINICAL PRESENTATION IN INFANCY:

The most distinctive seizure subtype is a prolonged hemiclonic seizure, although not all patients experience this seizure type.3

Other common seizure types in the first 2 years include myoclonic and generalized tonic-clonic seizures.3

Seizures often evolve into status epilepticus.6

12 M 2 Years1 M1 M

12 M 2 Years1 M1 M

12 M 2 Years1 M1 M

Seizures typically develop in the first year of life in infants who have otherwise been developing normally.3,5

Dravet syndrome has a broad differential diagnosis but has unique clinical characteristics

to confirm a correct diagnosis6,8:

Temperature sensitivity

Developmental delays following early

normal development

Prolonged seizures in an otherwise normally

developing infant

Myoclonic seizures

EARLY CHILDHOODDuring the second year of life3,6: EEG abnormalities may emerge.

While the child has normal cognitive development prior to seizure activity, cognitive deficits emerge between 18 months and 5 years of age.3,6 Children have moderate to severe intellectual disability and slow language progression during the second year of life.

Children frequently present to the emergency department with status epilepticus, which can lead to5,6,11,12:

Brain edema

Brain herniation

Death

2 YEARS

8 YEARS

Impaired oculomotor coordination, dysarthria, oral motor skill deficits, impaired communication5,9

Crouched gait, hypotonia, incoordination, impaired dexterity3

Lower height/weight compared with peers10

CLINICAL PRESENTATION AFTER AGE 2:

Myoclonic, focal impaired awareness, and atypical absence seizures3

Obtundation status3,*

Seizures triggered by...

Hyperthermia

Flashing lights

Visual patterns

Bathing

Emotional stress

Overexertion

8 Years1 M 12 M 2 Years 3 Years 10 Years 12 Years 12 Years1 M 4 Years 8 Years 12 Years 18 Years

8 Years1 M 12 M 2 Years 3 Years 10 Years 12 Years 12 Years1 M 4 Years 8 Years 12 Years 18 Years

8 Years1 M 12 M 2 Years 3 Years 10 Years 12 Years 12 Years1 M 4 Years 8 Years 12 Years 18 Years

8 Years1 M 12 M 2 Years 3 Years 10 Years 12 Years 12 Years1 M 4 Years 8 Years 12 Years 18 Years

DRAVET SYNDROME AFFECTS MOTOR AND COGNITIVE DEVELOPMENT

*Usually occurs in children older than 2 years; typically observed as nonconvulsive status epilepticus in younger children.

ADOLESCENCE/ ADULTHOODSeizures persist, occurring more often during sleep.5

Sudden unexpected death in epilepsy (SUDEP) is not uncommon in children with

Dravet syndrome.14

7% to 18% mortality rate in patients under 18 years1,15

SUDEP is the leading cause of death.14

Risk factors for SUDEP include treatment- resistant generalized tonic-clonic seizures,

developmental delay, and polytherapy.14

CLINICAL PRESENTATION IN ADOLESCENCE:

Nocturnal generalized tonic-clonic seizures with focal onset3,5

8 Years1 M 12 M 2 Years 3 Years 10 Years 12 Years 12 Years1 M 4 Years 8 Years 12 Years 18 Years

ADOLESCENCE

ADULTHOOD

Ataxia and crouch gait3

Increased risk of SUDEP (although SUDEP can occur at any time)5,11,13

Motor signs include3,5,8,16:

• Intention tremor • Extrapyramidal rigidity

• Walking difficulties (including crouched gait) • Balance problems

SIGNS AND SYMPTOMS EVOLVE OVER TIME, MAKING RECOGNITION DIFFICULT IN ADOLESCENCE/ADULTHOOD IF THE PATIENT HAS NOT BEEN PREVIOUSLY DIAGNOSED

Behavioral disorders are observed5:

• Attention deficits/hyperactivity • Oppositional and personality

disorders

• Autistic traits • Psychotic features

Signs and symptoms include3,6,17:

• Sleep disturbance

• Decreased response to pain

• Delayed dental development

• Dysphagia

• Intolerance of heat and cold

• Constipation

Time is of the essence Given the severity of seizures, including status epilepticus, and the increased risk of SUDEP in patients with Dravet syndrome, early and accurate diagnosis is urgently needed.

What to do if you suspect Dravet syndrome?

To find a Dravet specialist or refer families, please visit www.dravetfoundation.org/find-a-doctor

References: 1. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Severe myoclonic epilepsy in infancy: Dravet syndrome. In: Delgado-Escueta AV, Guerrini R, Medina MT, Genton P, Bureau M, Dravet C, eds. Advances in Neurology. Myoclonic Epilepsies. Vol 95. Philadelphia, PA: Lippincott Williams & Wilkins; 2005. 2. Wu YW, Sullivan J, McDaniel SS, et al. Incidence of Dravet syndrome in a US population. Pediatrics. 2015;136(5):e1310-e1315. 3. Wirrell EC, Laux L, Donner E, et al. Optimizing the diagnosis and management of Dravet syndrome: recommendations from a North American consensus panel. Pediatr Neurol. 2017;68:18-34.e13. 4. Akiyama M, Kobayashi K, Yoshinaga H, Ohtsuka Y. A long-term follow-up study of Dravet syndrome up to adulthood. Epilepsia. 2010;51(6):1043-1052. 5. Van Dam V, Korff CM. Dravet syndrome: an update. Schweiz Arch Neurol Psychiatr. 2013;164(5):153-157. 6. Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011;52(suppl 2):3-9. 7. Cetica V, Chiari S, Mei D, et al. Clinical and genetic factors predicting Dravet syndrome in infants with SCN1A mutations. Neurology. 2017;88(11):1037-1044. 8. Scheffer IE. Diagnosis and long-term course of Dravet syndrome. Eur J Paediatr Neurol. 2012;16(suppl 1):S5-S8. 9. Cassé-Perrot C, Wolff M, Dravet C. Neuropsychological aspects of severe myoclonic epilepsy in infancy. In: Jambaqué I, Lassonde M, Dulac O, eds. Neuropsychology of Childhood Epilepsy. Boston, MA: Springer US; 2001:131-140. 10. Eschbach K, Scarbro S, Juarez-Colunga E, Allen V, Hsu S, Knupp K. Growth and endocrine function in children with Dravet syndrome. Seizure. 2017;52:117-122. 11. Thom M, Michalak Z, Wright G, et al. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings. Neuropathol Appl Neurobiol. 2016;42(5):463-476. 12. Ceulemans B. Overall management of patients with Dravet syndrome. Dev Med Child Neurol. 2011;53(suppl 2):19-23. 13. Smithson WH, Colwell B, Hanna J. Sudden unexpected death in epilepsy: addressing the challenges. Curr Neurol Neurosci Rep. 2014;14(12):502. 14. Cooper MS, McIntosh A, Crompton DE, et al. Mortality in Dravet syndrome. Epilepsy Res. 2016;128:43-47. 15 Skluzacek JV, Watts KP, Parsy O, Wical B, Camfield P. Dravet syndrome and parent associations: the IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia. 2011;52(suppl 2):95-101. 16. Genton P, Velizarova R, Dravet C. Dravet syndrome: the long-term outcome. Epilepsia. 2011;52:44-49. 17. Villas N, Meskis MA, Goodliffe S. Dravet syndrome: characteristics, comorbidities, and caregiver concerns. Epilepsy Behav. 2017;74:81-86. 18. Chiron C, Dulac O. The pharmacologic treatment of Dravet syndrome. Epilepsia. 2011;52(suppl 2):72-75.

Increased emergency

department visits to treat

status epilepticus12

Seizures persist

despite standard AED treatment16

Seizures may be worsened

by AEDs that target

sodium channels12,18

INAPPROPRIATE TREATMENT POSES SIGNIFICANT RISKS TO PATIENTS

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